Molecular modeling of manganese regulation of calmodulin-sensitive adenylyl cyclase from mammalian sperm.
Abstract: The soluble calmodulin-sensitive isoform of adenylyl cyclase isolated from equine sperm is unique because it requires Mn(2+) rather than Mg(2+) for activity. To gain insight into the molecular action of metals on sperm adenylyl cyclase, the kinetics of Mn(2+) and ATP effect was examined. A biphasic response to increases in ATP concentration was observed when metal was held constant. When [Mn(2+)] exceeded [ATP], however, greatly enhanced enzyme activity was observed. The kinetic profiles were consistent with allosteric activation of adenylyl cyclase by Mn(2+). Linear transformation of the data yielded an apparent K(m) for Mn-ATP of 5.8 mM and calculated V(max) of 12 nM cyclic AMP formed/min/mg. Data analysis using calculated equilibrium concentrations of free and complexed reactants provided similar estimates of these kinetic parameters.
Publication Date: 2003-11-25 PubMed ID: 14630024DOI: 10.1016/j.bbrc.2003.09.215Google Scholar: Lookup
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Summary
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The research investigated the unique characteristic of the calmodulin-sensitive adenylyl cyclase in equine sperm, which relies on manganese ions for activity rather than magnesium ions, typically used by most organisms. The study focused on examining the kinetics of manganese and ATP interaction and their effects on adenylyl cyclase regulation.
Understanding Adenylyl Cyclase
- In human and other mammalian bodies, adenylyl cyclase is a crucial enzyme that aids in multiple signal transduction pathways. It is responsible for converting ATP (adenosine triphosphate) into cyclic AMP and pyrophosphate, which are vital for a range of physiological processes. Typically, this enzyme relies on magnesium ions for its activation.
- However, in the equine sperm, a unique isoform of the enzyme, the calmodulin-sensitive adenylyl cyclase, requires manganese ions, not magnesium ions, for activation. This discovery drove the direction of the research.
Focus of The Study
- The research primarily focused on the kinetic behavior of manganese ions (Mn2+) and ATP (adenosine triphosphate).
- Part of the study concentrated on determining how changes in ATP concentration affect enzyme activity when the concentration of manganese is kept constant.
- The researchers also studied the effects when the concentration of manganese exceeds that of ATP.
Findings of the Research
- Observations showed that the response to increases in ATP concentration displayed a biphasic mode. This means the reaction proceeds in two phases with different rates.
- The study found that when the manganese concentration exceeded the ATP concentration, there was a substantial increase in enzyme activity.
- The kinetic data patterns pointed towards allosteric activation of adenylyl cyclase being induced by manganese ions. Allosteric activation is a process where the activity of an enzyme is regulated through the binding of an effector molecule at a site other than the enzyme’s active site. In this case, manganese ions serve as allosteric activators.
- After performing a linear transformation of the data, an apparent Km (Michaelis constant) of 5.8 mM for the Mn-ATP was calculated. Km is a measure of the substrate concentration at which an enzyme achieves half of its maximum reaction speed. A higher Km value typically means steeper concentration gradients are required to achieve maximum speed.
- The calculated maximum velocity (Vmax) was 12 nM of cyclic AMP formed per minute per mg. Vmax represents the maximum rate of product formation by an enzyme when it is fully saturated with the substrate.
Cite This Article
APA
Toscano WA, Toscano JS, Toscano DG, Gross MK.
(2003).
Molecular modeling of manganese regulation of calmodulin-sensitive adenylyl cyclase from mammalian sperm.
Biochem Biophys Res Commun, 312(1), 91-96.
https://doi.org/10.1016/j.bbrc.2003.09.215 Publication
Researcher Affiliations
- Division of Environmental and Occupational Health, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA. tosca001@umn.edu
MeSH Terms
- Adenosine Triphosphate / chemistry
- Adenylyl Cyclases / chemistry
- Adenylyl Cyclases / metabolism
- Animals
- Coenzymes / chemistry
- Computer Simulation
- Enzyme Activation
- Horses
- Kinetics
- Male
- Manganese / chemistry
- Models, Chemical
- Models, Molecular
- Spermatozoa / chemistry
- Spermatozoa / enzymology
- Structure-Activity Relationship
- Substrate Specificity
Citations
This article has been cited 1 times.- Schultz ACF, Landau M, Lupas AN, Schultz JE. Lipid regulation of adenylyl cyclase Rv1625c from Mycobacterium tuberculosis by its membrane-domain receptor. FEBS J 2025 Oct;292(19):5234-5243.
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